Table 1.
Antagonist activity of 2027 and 018 plus GABA agonist potencies at selected GABAΑ receptor subtypes determined in the FMP assay.
| Receptor | 2027 (IC50 (μM), pIC50 ± SEM, n) | 018 (IC50 (μM), pIC50 ± SEM, n) | GABA (EC50 (μM), pEC50 ± SEM, n) | GABA EC80, μM | |||
|---|---|---|---|---|---|---|---|
| α1β2δ | 6.68 | (5.17 ± 0.10, 3) | 0.24 | (6.61 ± 0.050, 4) | 6.71 | (5.17 ± 0.087, 4)a | 10–14 |
| α1β2γ2 | 4.96 | (5.30 ± 0.17, 4) | 0.79 | (6.10 ± 0.11, 4) | 1.71 | (5.77 ± 0.022, 3) | 8.0 |
| α2β2γ2 | 2.96 | (5.53 ± 0.19, 3) | 0.32 | (6.49 ± 0.13, 3) | 1.47 | (5.83 ± 0.045, 3) | 10 |
| α3β2γ2 | 0.29 | (6.54 ± 0.17, 3) | 0.079 | (7.10 ± 0.18, 3) | 2.21 | (5.63 ± 0.11, 3) | 10 |
| α4β1δ | 1.03 | (5.99 ± 0.028, 3) | 0.088 | (7.06 ± 0.11, 4) | 0.17 | (6.77 ± 0.11, 3) | 0.27–1.0 |
| α4β1γ2 | 0.17 | (6.78 ± 0.081, 3) | 0.037 | (7.43 ± 0.094, 3) | 1.40 | (5.86 ± 0.014, 3) | 4.0–8.0 |
| α4β2δ | 0.36 | (6.44 ± 0.12, 3) | 0.068 | (7.17 ± 0.080, 3) | 0.25 | (6.61 ± 0.030, 3)a | 0.80–1.0 |
| α5β2γ2 | 0.59 | (6.23 ± 0.19, 4) | 0.051 | (7.29 ± 0.19, 4) | 0.47 | (6.33 ± 0.20, 3) | 3.0 |
| α6β2δ | 4.13 | (5.38 ± 0.050, 3) | 0.33 | (6.48 ± 0.082, 3) | 0.21 | (6.68 ± 0.13, 3)a | 3.0 |
The antagonist activity was determined using the stated GABA EC80 concentration calculated from the determined GABA potencies.
IC50/EC50 values are determined from concentration response curves and given as means. aData from L’Estrade et al.49.